Graft versus Host Disease (GVHD) is a major debilitating, and potentially lethal, side effect of bone marrow transplantation. It occurs when lymphocytes from the donor present in the bone marrow inoculums attack and destroy healthy tissues of the recipient. It is thought that GVHD is however useful to eliminate residual tumors persisting after chemical treatments. Biological means to better manage GVHD will therefore have a major impact on public health.
Among numerous costimulatory signals necessary for T cell activation, the inhibition of ICOS-LICOS interaction has been shown to prevent or delay GVHD in mice models (Taylor et al. (2005) Blood 105(8): 3372-3380).
The current treatments for GVHD are intravenously administered glucocorticoids, such as prednisone. The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse.
Therefore, there is still a great need for providing efficient therapeutic strategies targeting GVHD, with lower side effects.
The inventors surprisingly found that a monoclonal antibody against human ICOS, called 314.8, significantly impacts a xenogenic GVHD (xeno-GVHD) induced after transfer of human cells into immunodeficient mice. Xeno-GVHD is a closer model of GVHD than mice models relative to the human disease. Thus, said antibody may constitute a promising therapeutic strategy of GVHD.